RT Journal Article
SR Electronic
T1 Apparent intramolecular acyl migration of zomepirac glucuronide.
JF Drug Metabolism and Disposition
JO Drug Metab Dispos
FD American Society for Pharmacology and Experimental Therapeutics
SP 469
OP 473
VO 10
IS 5
A1 Hasegawa, J
A1 Smith, P C
A1 Benet, L Z
YR 1982
UL http://dmd.aspetjournals.org/content/10/5/469.abstract
AB For the antiinflammatory drug zomepirac (Z), 5-(4-chlorobenzoyl)-1,4-dimethyl-1H-pyrrole-2 acetic acid, the glucuronic acid conjugate (ZG) is the major metabolite. During analytical development ZG was found to be unstable at physiological pH, leading to four compounds other than Z. ZG and the other fractions were purified from urine by preparative HPLC and the structure of ZG was confirmed by elemental analysis and by NMR and mass spectrometry. Fast atom bombardment mass spectrometry was used to analyze the unstable, underivatized acyl glucuronides. ZG was cleaved by beta-glucuronidase but the other fractions were not. The stability of ZG was determined over a pH range of 1-8; the half-life was 27 min at pH 7.4 and 37 degrees C in water; maximum stability was found at pH 2. Intramolecular acyl migration of the glucuronide is postulated, as four of the isolated fractions formed from ZG yielded a mass-spectral parent ion corresponding to ZG+ H. The importance of sample handling prior to analysis to avoid acyl migration is emphasized.